Direct Versus Indirect Effect of Amino Acids on Hepatokines

NCT06240039 | Active Not Recruiting

• 1 other identifier: Diaakine
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Liver hormones are key metabolic regulators and increased in metabolic diseases, including fatty liver disease. The underlying mechanisms driving the elevated levels are currently unknown and presents a major challenge in understanding the interplay between liver hormones and fatty liver disease. The project aims to investigate what stimulates the liver to secrete its hormones and why the secretion is increased in patients with fatty liver disease. The investigator (Associate Prof. Nicolai J Wewer Albrechtsen) will investigate the direct and indirect effects of an amino acid amino infusion on the secretion of hepatokines in individuals with and without metabolic dysfunction-associated steatotic liver disease (MASLD).

Conditions

Non-Alcoholic Fatty Liver Disease; Obesity

Outcome Measures

Primary Outcomes (1)

• The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of follistatin.

  Defined as the difference in incremental AUC0-300 min (iAUC) of follistatin between study day B and study day C in healthy individuals.

  From blood sample at minute 0 until blood sample at minute 300.

Secondary Outcomes (6)

• The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of FGF21 and GDF15

  From blood sample at minute 0 until blood sample at minute 300.

• The direct versus the indirect effect of amino acids on circulating levels of hepatokines (follistatin, FGF21 and GDF15).

  From blood sample at minute 0 until blood sample at minute 300

• Differences between healthy and MASLD in the increase in hepatokines during study day B (direct effect of amino acids)

  From blood sample at minute 0 until blood sample at minute 300

• Differences between healthy and MASLD in the increase in hepatokines during study day C (indirect effect of amino acids).

  From blood sample at minute 0 until blood sample at minute 300

• The inhibitory effect of somatostatin versus the stimulatory effect of amino acids on glucagon, insulin and C-peptide levels during study day B in healthy and MASLD.

  From blood sample at minute -75 until blood sample at minute 45

Study Arms (1)

Evaluating the direct and indirect effect of amino acids on the regulation of hepatokines

EXPERIMENTAL

Participants will be subjected to four experimental days

Other: Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon

Interventions

Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon OTHER

The experimental days consist of four study days: 1. Assessment of liver fat and visceral fat by magnetic resonance imaging (MRI; 6-point Dixon) (study day A) 2. Somatostatin infusion (4 hours) plus amino acid infusion (45 minutes) (study day B) 3. Saline infusion (4 hours) plus amino acid infusion (45 minutes) (study day C) 4. Somatostatin infusion (4 hours) plus saline infusion (45 minutes) (study day D) The subjects will participate in the experimental days (study day B to D) in randomized order on three different days. For study day B to D, at timepoint t = -75, subjects will receive either; a 240-minute intravenous infusion of a somatostatin analogue (at 200 ng/kg/min (infusion rate will not exceed 1000 µg/hour) or saline. After 75 minutes (timepoint t = 0), the subjects will receive a 45-minute intravenous infusion of amino acids or saline at 3.885 ml/kg/hour. In total, blood will be sampled 11 times over a period of 6 hours and 15 minutes.

Evaluating the direct and indirect effect of amino acids on the regulation of hepatokines

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 25-65 years of age at time of screening
• Body mass index of 18.6-25 kg/m2

You may not qualify if:

• Contraindications for MRI-scan
• Severe liver disease (estimated by FIB4 score \> 3.25)
• Type 2 diabetes according to ADA criteria
• Significant history of alcoholism or drug/chemical abuse as per investigators judgement
• Amino acid related diseases
• Kidney disease
• Cardiac problems
• Cancer within the past 1 year
• Anemia
• Pregnancy or breast feeding
• Smoking
• Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
• Group 2 (individuals with hepatic steatosis):
• Male or female between 25-65 years of age at time of screening
• Body mass index of 25-40 kg/m2

Sponsors & Collaborators

• University of Copenhagen: lead
• Bispebjerg Hospital: collaborator

Study Sites (1)

Bispebjerg University Hospital

Copenhagen, Denmark

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD, PhD

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: February 11, 2024
• Primary Completion: April 16, 2025
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)